It is our hypothesis that UHB-flanked genes contribute to immune evasion in the Lyme disease spirochetes (LDS). Previous studies of the closely related ospE gene family have demonstrated that genetic polymorphisms develop during infection in mice and that these OspE variants are antigenically distinct. To address our hypothesis, the genetic stability of the ospF and Family 163 genes during infection in mice will be analyzed by infecting mice with an isogenic population of spirochetes of known genetic composition. Isogenic clones will be recovered three months post-infection and their UHB-flanked genes will be analyzed using a combination of PCR and DNA sequencing approaches. The temporal pattern and specificity of the humoral immune response to variant proteins will be assessed using sera collected from mice during the course of infection. These studies will increase our understanding of the mechanisms utilized by LDS to maintain chronic infection, which can lead to neuroborreliosis, and maintain populations in their animal reservoirs.